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The opium poppy is a natural source of opioids such as morphine. Although they are revered for their potent pain-relieving effects, when used chronically, opioids can lead to analgesic tolerance, hyperalgesia and withdrawal. Burma et al. (p 355) show that pannexin-1 (Panx1) channels on spinal microglia are essential for opioid withdrawal, and that blocking Panx1 can alleviate opioid withdrawal in rodents. Puig and Gutstein (p 272) discuss these findings alongside those recently reported by Corder et al. in the February issue of Nature Medicine. Illustration credit: Nicole Burma, Trang laboratory.
The scientific process relies on people's willingness to publish data-driven findings. Turning to the legal system to adjudicate the merit of evidence-based assertions in the scientific literature leads us down a dangerous path.
Two new studies show that mechanisms mediating the opioid side effects of tolerance, hyperalgesia and physical dependence are mediated spinally and can be dissociated from analgesia. These side effects can be selectively targeted by clinically available drugs without affecting their pain-relieving effects.
A recent study shows that microbial-community structure and function substantially expand and diversify in all body sites from birth to age 4–6 weeks. It then resembles microbiota from its corresponding maternal body site, independently of the infant's mode of delivery or other prenatal factors.
In a recent study in mice, researchers combined tumor barcoding with unbiased genomic analysis and identified Cd109 as a hub gene involved in metastatic progression. They show that pharmacological inhibition of its downstream effectors JAK1 and STAT3 curtails metastatic growth.
A new study shows that nicotinic receptors activate a particular type of interneuron in the prefrontal cortex. Deficits in this relationship give rise to behavioral abnormalities similar to those associated with schizophrenia, which can be ameliorated by nicotine.
Excess urinary cystine can lead to painful stone formation. There is no current effective treatment, but here Pankaj Kapahi, Marshall Stoller and colleagues have found that α-lipoic acid can prevent or even reverse formation of these stones in a mouse model.
In vivo screening of pro-metastatic factors in a genetically engineered mouse model of lung cancer uncovered the CD109–JAK–STAT3 axis as a key contributor of metastatic dissemination of lung cancer cells. Activation of this pathway predicts poor outcome in patients with cancer, and its pharmacological inhibition dramatically reduces the metastatic ability of tumor cells, suggesting that it might be an effective intervention in patients.
Transcriptomic and metabolic profiling reveals that the creatine kinase pathway is essential for growth of acute myeloid leukemias expressing the transcription factor EVI1.
Whole-genome shotgun sequencing and sequencing of the gene encoding the 16S rRNA in samples from a variety of body sites in a large cohort of mothers and their infants reveals that, during the 6 weeks after birth, changes in the composition and function of the microbiome are driven by body site but not by the mode of delivery.
Carlo Ferrari and colleagues reveal that hepatitis B virus (HBV) specific CD8 T cells from individuals with chronic HBV infections have extensive mitochondrial dysfunction that contributes to impaired antiviral activity but can be targeted with antioxidants.
Xin Lin and colleagues report that JNK1 negatively regulates immune responses against Candida albicans infection by inhibiting CD23 expression and subsequent nitric oxide production, which mediate antifungal resistance in JNK1-deficient mice.
In transgenic mouse models of neuropsychiatric disease, loss of nicotinic cholinergic signaling in cortical inhibitory interneurons causes neurocognitive behavioral deficits and reduced neuronal activity in prefrontal circuits. Chronic administration of nicotine can restore this cortical hypofrontality phenotype.
The release of ATP from spinal microglia via pannexin-1 channels is required for withdrawal symptoms after termination of chronic opioid treatment in rodents, and pharmacological blockade of pannexin-1 channels reduces the severity of withdrawal without affecting opiate analgesia.
Intracellular trafficking of the voltage-gated cardiac Na+ channel Nav1.5 is regulated by lysine deacetylation mediated by Sirt1, thereby affecting sodium current and cardiac electrical activity.
A previously uncharacterized population of innate lymphoid cells (ILCs) in the tumor microenvironment limits T cell expansion and cytokine production, and associates with early recurrence in patients with cancer. Depletion of this regulatory immunosuppressive cell population overcomes this effect, suggesting important implications for cancer immunotherapy.
A method enabling copy-number analysis of single cells from formalin-fixed paraffin-embedded samples is described, validated and applied to analyze samples of synchronous ductal carcinoma in situ and invasive breast carcinoma.
DNA methylation sequencing and bioinformatic analyses uncover an epigenetic disease spectrum in Ewing sarcoma. These characteristic epigenome patterns correlate with state of differentiation and disease aggressiveness, and pave the way for the development of biomarkers.